Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that affects an estimated 5 million people worldwide, with incidence continuing to rise globally. The disease causes debilitating symptoms such as abdominal pain, bloody diarrhea, and urgent bowel movements. While conventional treatments have improved patient outcomes, many carry risks such as immunosuppression, liver toxicity, and increased susceptibility to infections. This has fueled growing interest in alternative therapies, and one of the most promising is spermidine.
A recent study in the International Journal of Biological Macromolecules highlights spermidine’s potential as a UC treatment. Researchers explored its anti-inflammatory, gut-protective properties using an innovative, localized hydrogel delivery system, demonstrating remarkable therapeutic versatility.
Spermidine mitigates ulcerative colitis through multi-targeted gut healing mechanisms.
In a mouse model of ulcerative colitis, rectal delivery of a spermidine hydrogel provided high local concentrations of spermidine directly to inflamed colonic tissue, leading to significant improvements in disease severity and mucosal healing.
Based on findings from Ouyang et al., 2025. © Melissa Cano, 2025.
What Is Ulcerative Colitis?
Ulcerative colitis (UC) is one of the two main forms of inflammatory bowel disease (IBD), a chronic, relapsing condition characterized by persistent inflammation of the gastrointestinal tract. Unlike Crohn’s disease, which can affect any part of the digestive system and often damages the full thickness of the intestinal wall, UC is confined to the colon and rectum and affects only the surface layer of the intestinal lining. This results in common symptoms such as bloody diarrhea, abdominal pain, and a frequent, urgent need to use the bathroom.
UC arises from a complex interaction between the immune system, the gut barrier, and the intestinal microbiome. Growing research shows that gut bacteria and the metabolites they produce play a key role in driving inflammation, making the health and balance of the gut ecosystem a central focus in developing new therapies. (For a deeper look at another recent study identifying a new polyamine with potential relevance here, explore this blog post.)
A Spermidine Hydrogel: Precision Delivery for the Inflamed Colon
In this new study, researchers developed a novel rectal spermidine hydrogel to target the inflamed colon in UC. This thermosensitive, mucoadhesive formulation transitions into a gel upon reaching the colon, allowing it to adhere firmly to ulcerated tissue and release spermidine gradually over several hours. By bypassing the upper digestive tract, the hydrogel delivers high local concentrations of spermidine directly to the site of inflammation, maintaining continuous therapeutic action while resisting intestinal movement and fluid flow.
How Spermidine Can Help Fight Ulcerative Colitis
The new study shows that spermidine delivered through this innovative hydrogel offers several key benefits in the treatment of UC:
- Activate autophagy: The spermidine hydrogel activated autophagy markers (LC3, ATG5, ATG7) and improved autophagic flux (the body’s natural “cellular recycling” process), promoting epithelial regeneration and mucosal healing.
- Repair the gut barrier: It strengthens the intestinal mucosal barrier by increasing tight junction proteins (ZO-1, occludin, claudin-5, which act like “seals” between gut cells) and mucin (MUC2, a protective mucus layer), helping prevent harmful substances from leaking into the body.
- Reduce inflammation: Spermidine reduces the secretion of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β) and increases anti-inflammatory cytokines like IL-10. It also promotes macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory (healing) M2 phenotype.
- Combat oxidative stress: Spermidine exhibits strong antioxidant activity, neutralizing free radicals and restoring antioxidant enzymes (CAT, SOD, GSH), which helps alleviate oxidative stress and cellular damage.
- Balance gut bacteria: Spermidine helps normalize intestinal dysbiosis by reducing harmful bacteria (e.g., Proteobacteria) and increasing beneficial bacteria (e.g., Firmicutes), improving gut microbiota composition and diversity.
- Improved colitis symptoms: In mice, spermidine alleviated key colitis symptoms, including weight loss, disease activity, and colonic mucosal damage.
Spermidine and the Future of Ulcerative Colitis Care
Spermidine continues to stand out as a remarkable, multi-targeted molecule with the power to support gut health, reduce inflammation, and promote mucosal healing in ulcerative colitis. This study demonstrates that innovative delivery methods, such as hydrogels, can enhance spermidine’s impact by targeting it directly to the inflamed colon, complementing the benefits of oral supplementation. By combining these approaches, we can fully harness spermidine’s therapeutic potential. With ongoing research and novel delivery strategies, spermidine offers exciting promise for improving UC management and nurturing overall intestinal wellness.
